LAUSR

BACKGROUND AND AIMS There are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD), between people with type 2 diabetes mellitus (T2DM) versus people without T2DM. We assessed the time to fibrosis progression in people with T2DM versus people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies. METHODS This study included 447 adult participants (64% female) with NAFLD who had paired liver biopsies >1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis, compared between participants with T2DM versus participants without T2DM. RESULTS The mean (±SD) age and BMI were 50.9 (±11.5) years and 34.7 (±6.3) kg/m2, respectively. The median (IQR) time between biopsies was 3.3 (1.8-6.1) years. Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4-years (24% versus 20%), 8-years (60% versus 50%), and 12-years (93% versus 76%), P=0.005. Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio 1.69, 95%CI 1.17 - 2.43, P=0.005). The cumulative incidence of fibrosis regression by ≥1 stage was similar between participants with T2DM versus participants without T2DM, (P=0.24). CONCLUSION In this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we demonstrate that fibrosis progresses faster in participants with T2DM compared to participants without T2DM. These data have important implications for clinical practice and trial design.